Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/87361
Title: Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells
Authors: Kitajima, Shojiro
Lee, Kian Leong
Hikasa, Hiroki
Sun, Wendi
Huang, Ruby Yun-Ju
Yang, Henry
Matsunaga, Shinji
Yamaguchi, Takehiro
Araki, Marito
Kato, Hiroyuki
Poellinger, Lorenz
Keywords: Hypoxia-inducible Factors
Ammonia
Issue Date: 2017
Source: Kitajima, S., Lee, K. L., Hikasa, H., Sun, W., Huang, R. Y.-J., Yang, H., et al. (2017). Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells. Oncotarget, 8(70), 114481-114494.
Series/Report no.: Oncotarget
Abstract: Ammonia is a toxic by-product of metabolism that causes cellular stresses. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism to survive against its toxicity have yet to be identified. We demonstrated that the hypoxia-inducible factor-1α (HIF-1α) is stabilized and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1α counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1α in a biphasic ammonia stress management in the cancer stem-like cells where GS facilitates cell proliferation and HIF-1α contributes to the metabolic remodeling in energy fuel usage resulting in attenuated proliferation but conversely promoting cell survival.
URI: https://hdl.handle.net/10356/87361
http://hdl.handle.net/10220/44412
DOI: 10.18632/oncotarget.23010
Rights: © 2017 The Author(s) (published by Impact Journals). This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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